The present invention relates to a device and a method for dispensing a radioactive liquid to a destination. In particular, the invention relates to the problem of accurately dispensing a well-determined dose of radioactivity, e.g., for injection to a living body.
In a number of medical applications, it is necessary to deliver a radiopharmaceutical containing a radionuclide to a patient. Due to the ionizing radiation emitted by the radionuclide, such pharmaceuticals pose a danger to both the patient and the personnel administering the radiopharmaceutical if not handled property.
Examples for diagnostic uses of radiopharmaceuticals include positron emission tomography (PET) and single-photon emission computerized tomography (SPECT). In these methods, a patient is injected a dose of a radiopharmaceutical which can be absorbed by certain cells in the brain or in other organs. The concentration of the accumulated radiopharmaceutical in a specific body part will often depend on factors of diagnostic interest, such as cell metabolism or other physiological or biochemical processes. Thus, such processes can be imaged in a non-invasive fashion by determining the spatio-temporal distribution of radioactivity within the body part of interest. In PET, this is achieved by monitoring pairs of temporally coincident gamma rays emitted in opposite directions resulting from the annihilation of positrons, which are emitted through beta-plus decays of the (proton-rich) radionuclide. The most common radionuclides (radioisotopes) for use with PET are 15O, 15F, 11C, 13N and 82Rb. Radiopharmaceuticals of interest for PET include, but are not limited to, substances like [15O]—H2O, [18F]-fluorodeoxyglucose ([18F]-FDG), [18F]-fluoromisonidazole ([18F]-FMISO), [11C]-labeled amino acids, [13N]-ammonia etc.
The most common therapeutic uses of radiopharmaceuticals are the 131I therapies in thyroid diseases.
In these applications, it is desirable to administer an exactly determined dose of radiopharmaceutical to the body. Often the radiopharmaceutical is delivered in a vial from which it has to be dispensed into individual patient doses. In many centers this is a manual process done by the technical personnel. Since the concentration of the radiopharmaceutical in the vial can be very high, the manual dispensing is associated with considerable radiation burden to the hands. Furthermore the accuracy of the manual dispensing is limited and dependent on the experience of the person in charge.
As an example, U.S. Pat. No. 4,410,108 discloses a syringe shield equipped with a radiation detector. A liquid radiopharmaceutical is drawn from a vial into the barrel of a syringe placed within the syringe shield, while the level of radioactivity within the barrel is monitored by the radiation detector. In this way, an aliquot of the radiopharmaceutical having exactly the required dose of radioactivity can be drawn into the syringe. Subsequently, the syringe with its shield is manually removed from the vial, and the radiopharmaceutical is injected to the patient. This device is unsatisfactory in requiring manual transfer of the syringe after it has been filled with the radiopharmaceutical, as this may expose the personnel handling the syringe to ionizing radiation. Although the half-life of the radiopharmaceutical is usually rather short and the applied dosages are themselves not harmful, constant and repeated exposure over an extended period of time can be harmful.
A number of techniques have been proposed to reduce exposure by minimizing the time of exposure of personnel, by maintaining distance between personnel and the source of radiation, and by shielding personnel from the source of radiation. As an example, European patent application EP 0 486 283 discloses a system for delivering H215O. A collection bottle is filled with saline, then a fluid stream comprising H215O is passed through the collection bottle while the activity in this bottle is monitored by a radiation detector. When a desired level of radiation is reached, the liquid in the bottle is transferred to a motor-driven syringe and then injected to the patient body. U.S. patent application publication No. 2003/0004463 also discloses a system for dispensing a radiopharmaceutical in a remote fashion, without the need of manual intervention. The radiopharmaceutical is drawn from a vial into a syringe surrounded by a radiation detector, and the level of radioactivity in the syringe is determined. Through specially adapted tubing and valves, the radiopharmaceutical is subsequently delivered to a patient without the need of moving the syringe to another location.
While these systems obviate the need of manual handling of a syringe, they tend to be imprecise in situations where small amounts of radioactive liquid, possibly with a very high concentration of activity, need to be handled, due to the presence of dead volumes. By the way of example, the radiopharmaceutical may come in a vial at an activity concentration of 2 GBq/ml (one billion Becquerels per milliliter). If the required activity for injection to the patient is, say, 100 MBq, a volume of just 50 microliters needs to be transferred from the vial to the patient. Such small amounts of liquid are difficult to handle with the systems of the prior art.
U.S. Pat. Nos. 4,562,829 and 4,585,000 disclose strontium-rubidium infusion systems equipped with an in-line radiation detector. A radiopharmaceutical exiting a strontium-rubidium generator flows past the radiation detector, which monitors the activity of the radiopharmaceutical in passing. From there, the radiopharmaceutical is either administered to a patient or is sent to waste. In U.S. Pat. No. 4,409,966, a flow of patient blood is shunted through a radiation detector during injection of the radiopharmaceutical, and the level of radioactivity in the blood is monitored. Also with such systems, it is difficult to administer an exactly determined dose, especially for concentrated radiopharmaceuticals with high specific activities, as the volume of the tubing already may exceed the desired volume to be injected.